Human papillomaviruses (HPV) have been associated with squamous cell carcinomas (SCC) of the skin in both the immunocompetent and the immunocompromised individual. A paucity of literature, however, exists concerning the presence of HPV in SCCs from patients with mycosis fungoides (MF)-[cutaneous T-cell lymphoma (CTCL.)]. We describe a case of multiple SCCs in which HPV DNA was detected over a 9-year period from a patient with MF. This patient with a long history of MF developed 7 small red scaly indurated lesions of sun and non-sun-exposed areas during a 9-year period (1981-1989). Histologic examination of all the lesions revealed that they were SCCs. The patient had no recorded history of arsenic exposure. To investigate the possible role of HPV as a co-carcinogen, we tested the 7 cases of SCC for HPV. Polymerase chain reaction (PCR) was performed on formalin-fixed tissue sections using HPV L.1 consensus sequence primers. Four of the 7 SCCs were positive for HPV DNA. These results suggest a possible role for HPV as a co-carcinogen in the development of SCCs in this patient.